--- _id: '10754' abstract: - lang: eng text: Targeting dysregulated Ca2+ signaling in cancer cells is an emerging chemotherapy approach. We previously reported that store-operated Ca2+ entry (SOCE) blockers, such as RP4010, are promising antitumor drugs for esophageal cancer. As a tyrosine kinase inhibitor (TKI), afatinib received FDA approval to be used in targeted therapy for patients with EGFR mutation-positive cancers. While preclinical studies and clinical trials have shown that afatinib has benefits for esophageal cancer patients, it is not known whether a combination of afatinib and RP4010 could achieve better anticancer effects. Since TKI can alter intracellular Ca2+ dynamics through EGFR/phospholipase C-γ pathway, in this study, we evaluated the inhibitory effect of afatinib and RP4010 on intracellular Ca2+ oscillations in KYSE-150, a human esophageal squamous cell carcinoma cell line, using both experimental and mathematical simulations. Our mathematical simulation of Ca2+ oscillations could fit well with experimental data responding to afatinib or RP4010, both separately or in combination. Guided by simulation, we were able to identify a proper ratio of afatinib and RP4010 for combined treatment, and such a combination presented synergistic anticancer-effect evidence by experimental measurement of intracellular Ca2+ and cell proliferation. This intracellular Ca2+ dynamic-based mathematical simulation approach could be useful for a rapid and cost-effective evaluation of combined targeting therapy drugs. acknowledgement: "This work was partially supported by grants from National Institutes of Health (NIH) (R01 CA185055, S10OD0252300) and The University of Texas System STARs Award (to Z.P.),\r\nThe University of Texas at Arlington Interdisciplinary Research Program (to B.C., H.V.K. and Z.P.). " article_number: '1763' article_processing_charge: Yes article_type: original author: - first_name: Yan full_name: Chang, Yan last_name: Chang - first_name: Marah full_name: Funk, Marah last_name: Funk - first_name: Souvik full_name: Roy, Souvik last_name: Roy - first_name: Elizabeth R full_name: Stephenson, Elizabeth R id: 2D04F932-F248-11E8-B48F-1D18A9856A87 last_name: Stephenson orcid: 0000-0002-6862-208X - first_name: Sangyong full_name: Choi, Sangyong last_name: Choi - first_name: Hristo V. full_name: Kojouharov, Hristo V. last_name: Kojouharov - first_name: Benito full_name: Chen, Benito last_name: Chen - first_name: Zui full_name: Pan, Zui last_name: Pan citation: ama: Chang Y, Funk M, Roy S, et al. Developing a mathematical model of intracellular Calcium dynamics for evaluating combined anticancer effects of afatinib and RP4010 in esophageal cancer. International Journal of Molecular Sciences. 2022;23(3). doi:10.3390/ijms23031763 apa: Chang, Y., Funk, M., Roy, S., Stephenson, E. R., Choi, S., Kojouharov, H. V., … Pan, Z. (2022). Developing a mathematical model of intracellular Calcium dynamics for evaluating combined anticancer effects of afatinib and RP4010 in esophageal cancer. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms23031763 chicago: Chang, Yan, Marah Funk, Souvik Roy, Elizabeth R Stephenson, Sangyong Choi, Hristo V. Kojouharov, Benito Chen, and Zui Pan. “Developing a Mathematical Model of Intracellular Calcium Dynamics for Evaluating Combined Anticancer Effects of Afatinib and RP4010 in Esophageal Cancer.” International Journal of Molecular Sciences. MDPI, 2022. https://doi.org/10.3390/ijms23031763. ieee: Y. Chang et al., “Developing a mathematical model of intracellular Calcium dynamics for evaluating combined anticancer effects of afatinib and RP4010 in esophageal cancer,” International Journal of Molecular Sciences, vol. 23, no. 3. MDPI, 2022. ista: Chang Y, Funk M, Roy S, Stephenson ER, Choi S, Kojouharov HV, Chen B, Pan Z. 2022. Developing a mathematical model of intracellular Calcium dynamics for evaluating combined anticancer effects of afatinib and RP4010 in esophageal cancer. International Journal of Molecular Sciences. 23(3), 1763. mla: Chang, Yan, et al. “Developing a Mathematical Model of Intracellular Calcium Dynamics for Evaluating Combined Anticancer Effects of Afatinib and RP4010 in Esophageal Cancer.” International Journal of Molecular Sciences, vol. 23, no. 3, 1763, MDPI, 2022, doi:10.3390/ijms23031763. short: Y. Chang, M. Funk, S. Roy, E.R. Stephenson, S. Choi, H.V. Kojouharov, B. Chen, Z. Pan, International Journal of Molecular Sciences 23 (2022). date_created: 2022-02-13T23:01:35Z date_published: 2022-02-01T00:00:00Z date_updated: 2023-08-09T10:17:07Z day: '01' ddc: - '510' - '576' department: - _id: HeEd doi: 10.3390/ijms23031763 external_id: isi: - '000754773500001' file: - access_level: open_access checksum: 8890ad20c54e90dc58ad5ea97c902998 content_type: application/pdf creator: dernst date_created: 2022-02-14T07:46:30Z date_updated: 2022-02-14T07:46:30Z file_id: '10756' file_name: 2022_IJMS_Chang.pdf file_size: 24416183 relation: main_file success: 1 file_date_updated: 2022-02-14T07:46:30Z has_accepted_license: '1' intvolume: ' 23' isi: 1 issue: '3' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '02' oa: 1 oa_version: Published Version publication: International Journal of Molecular Sciences publication_identifier: eissn: - '14220067' issn: - '16616596' publication_status: published publisher: MDPI quality_controlled: '1' scopus_import: '1' status: public title: Developing a mathematical model of intracellular Calcium dynamics for evaluating combined anticancer effects of afatinib and RP4010 in esophageal cancer tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 23 year: '2022' ... --- _id: '9906' abstract: - lang: eng text: Endometriosis is a common gynecological disorder characterized by ectopic growth of endometrium outside the uterus and is associated with chronic pain and infertility. We investigated the role of the long intergenic noncoding RNA 01133 (LINC01133) in endometriosis, an lncRNA that has been implicated in several types of cancer. We found that LINC01133 is upregulated in ectopic endometriotic lesions. As expression appeared higher in the epithelial endometrial layer, we performed a siRNA knockdown of LINC01133 in an endometriosis epithelial cell line. Phenotypic assays indicated that LINC01133 may promote proliferation and suppress cellular migration, and affect the cytoskeleton and morphology of the cells. Gene ontology analysis of differentially expressed genes indicated that cell proliferation and migration pathways were affected in line with the observed phenotype. We validated upregulation of p21 and downregulation of Cyclin A at the protein level, which together with the quantification of the DNA content using fluorescence-activated cell sorting (FACS) analysis indicated that the observed effects on cellular proliferation may be due to changes in cell cycle. Further, we found testis-specific protein kinase 1 (TESK1) kinase upregulation corresponding with phosphorylation and inactivation of actin severing protein Cofilin, which could explain changes in the cytoskeleton and cellular migration. These results indicate that endometriosis is associated with LINC01133 upregulation, which may affect pathogenesis via the cellular proliferation and migration pathways. acknowledgement: "Open access funding provided by Medical University of Vienna. The authors would like to thank all the participants and health professionals involved in the present study. We want to thank our technical assistants Barbara Widmar and Matthias Witzmann-Stern for their diligent work and constant assistance. We would like to thank Simon Hippenmeyer for access to\r\nbioinformatic infrastructure and resources." article_number: '8385' article_processing_charge: Yes article_type: original author: - first_name: Iveta full_name: Yotova, Iveta last_name: Yotova - first_name: Quanah J. full_name: Hudson, Quanah J. last_name: Hudson - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Katharina full_name: Proestling, Katharina last_name: Proestling - first_name: Isabella full_name: Haslinger, Isabella last_name: Haslinger - first_name: Lorenz full_name: Kuessel, Lorenz last_name: Kuessel - first_name: Alexandra full_name: Perricos, Alexandra last_name: Perricos - first_name: Heinrich full_name: Husslein, Heinrich last_name: Husslein - first_name: René full_name: Wenzl, René last_name: Wenzl citation: ama: Yotova I, Hudson QJ, Pauler F, et al. LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line. International Journal of Molecular Sciences. 2021;22(16). doi:10.3390/ijms22168385 apa: Yotova, I., Hudson, Q. J., Pauler, F., Proestling, K., Haslinger, I., Kuessel, L., … Wenzl, R. (2021). LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms22168385 chicago: Yotova, Iveta, Quanah J. Hudson, Florian Pauler, Katharina Proestling, Isabella Haslinger, Lorenz Kuessel, Alexandra Perricos, Heinrich Husslein, and René Wenzl. “LINC01133 Inhibits Invasion and Promotes Proliferation in an Endometriosis Epithelial Cell Line.” International Journal of Molecular Sciences. MDPI, 2021. https://doi.org/10.3390/ijms22168385. ieee: I. Yotova et al., “LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line,” International Journal of Molecular Sciences, vol. 22, no. 16. MDPI, 2021. ista: Yotova I, Hudson QJ, Pauler F, Proestling K, Haslinger I, Kuessel L, Perricos A, Husslein H, Wenzl R. 2021. LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line. International Journal of Molecular Sciences. 22(16), 8385. mla: Yotova, Iveta, et al. “LINC01133 Inhibits Invasion and Promotes Proliferation in an Endometriosis Epithelial Cell Line.” International Journal of Molecular Sciences, vol. 22, no. 16, 8385, MDPI, 2021, doi:10.3390/ijms22168385. short: I. Yotova, Q.J. Hudson, F. Pauler, K. Proestling, I. Haslinger, L. Kuessel, A. Perricos, H. Husslein, R. Wenzl, International Journal of Molecular Sciences 22 (2021). date_created: 2021-08-15T22:01:27Z date_published: 2021-08-04T00:00:00Z date_updated: 2023-08-11T10:34:13Z day: '04' ddc: - '570' department: - _id: SiHi doi: 10.3390/ijms22168385 external_id: isi: - '000689147400001' file: - access_level: open_access checksum: be7f0042607ca60549cb27513c19c6af content_type: application/pdf creator: asandaue date_created: 2021-08-16T09:29:17Z date_updated: 2021-08-16T09:29:17Z file_id: '9922' file_name: 2021_InternationalJournalOfMolecularSciences_Yotova.pdf file_size: 2646018 relation: main_file success: 1 file_date_updated: 2021-08-16T09:29:17Z has_accepted_license: '1' intvolume: ' 22' isi: 1 issue: '16' language: - iso: eng month: '08' oa: 1 oa_version: Published Version publication: International Journal of Molecular Sciences publication_identifier: eissn: - '14220067' issn: - '16616596' publication_status: published publisher: MDPI quality_controlled: '1' scopus_import: '1' status: public title: LINC01133 inhibits invasion and promotes proliferation in an endometriosis epithelial cell line tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 22 year: '2021' ... --- _id: '9907' abstract: - lang: eng text: 'DivIVA is a protein initially identified as a spatial regulator of cell division in the model organism Bacillus subtilis, but its homologues are present in many other Gram-positive bacteria, including Clostridia species. Besides its role as topological regulator of the Min system during bacterial cell division, DivIVA is involved in chromosome segregation during sporulation, genetic competence, and cell wall synthesis. DivIVA localizes to regions of high membrane curvature, such as the cell poles and cell division site, where it recruits distinct binding partners. Previously, it was suggested that negative curvature sensing is the main mechanism by which DivIVA binds to these specific regions. Here, we show that Clostridioides difficile DivIVA binds preferably to membranes containing negatively charged phospholipids, especially cardiolipin. Strikingly, we observed that upon binding, DivIVA modifies the lipid distribution and induces changes to lipid bilayers containing cardiolipin. Our observations indicate that DivIVA might play a more complex and so far unknown active role during the formation of the cell division septal membrane. ' acknowledged_ssus: - _id: Bio - _id: LifeSc acknowledgement: "We thank Daniela Krajˇcíkova, Katarína Muchová, Zuzana Chromíkova and other members of Barák’s laboratory for useful discussions, suggestions and help. Special thanks also to Emília Chovancová for technical support. We are grateful to Juraj Labaj for drawing the model and for help with graphics. Many thanks to all members of Loose’s laboratory: Maria del Mar\r\nLópez, Paulo Caldas, Philipp Radler, and other members of the Loose’s laboratory for sharing their knowledge of SLB preparation and TIRF experiment chambers, for sharing coverslips and for help with the TIRF microscope and data analysis. We also thank the members of the Dept. of Biochemistry of Biomembranes at the Institute of Animal Biochemistry and Genetics, CBs SAS for their help with preparing the lipid mixtures. We thank J. Bauer for critically reading the manuscript." article_number: '8350' article_processing_charge: Yes article_type: original author: - first_name: Naďa full_name: Labajová, Naďa last_name: Labajová - first_name: Natalia S. full_name: Baranova, Natalia S. id: 38661662-F248-11E8-B48F-1D18A9856A87 last_name: Baranova orcid: 0000-0002-3086-9124 - first_name: Miroslav full_name: Jurásek, Miroslav last_name: Jurásek - first_name: Robert full_name: Vácha, Robert last_name: Vácha - first_name: Martin full_name: Loose, Martin id: 462D4284-F248-11E8-B48F-1D18A9856A87 last_name: Loose orcid: 0000-0001-7309-9724 - first_name: Imrich full_name: Barák, Imrich last_name: Barák citation: ama: Labajová N, Baranova NS, Jurásek M, Vácha R, Loose M, Barák I. Cardiolipin-containing lipid membranes attract the bacterial cell division protein diviva. International Journal of Molecular Sciences. 2021;22(15). doi:10.3390/ijms22158350 apa: Labajová, N., Baranova, N. S., Jurásek, M., Vácha, R., Loose, M., & Barák, I. (2021). Cardiolipin-containing lipid membranes attract the bacterial cell division protein diviva. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms22158350 chicago: Labajová, Naďa, Natalia S. Baranova, Miroslav Jurásek, Robert Vácha, Martin Loose, and Imrich Barák. “Cardiolipin-Containing Lipid Membranes Attract the Bacterial Cell Division Protein Diviva.” International Journal of Molecular Sciences. MDPI, 2021. https://doi.org/10.3390/ijms22158350. ieee: N. Labajová, N. S. Baranova, M. Jurásek, R. Vácha, M. Loose, and I. Barák, “Cardiolipin-containing lipid membranes attract the bacterial cell division protein diviva,” International Journal of Molecular Sciences, vol. 22, no. 15. MDPI, 2021. ista: Labajová N, Baranova NS, Jurásek M, Vácha R, Loose M, Barák I. 2021. Cardiolipin-containing lipid membranes attract the bacterial cell division protein diviva. International Journal of Molecular Sciences. 22(15), 8350. mla: Labajová, Naďa, et al. “Cardiolipin-Containing Lipid Membranes Attract the Bacterial Cell Division Protein Diviva.” International Journal of Molecular Sciences, vol. 22, no. 15, 8350, MDPI, 2021, doi:10.3390/ijms22158350. short: N. Labajová, N.S. Baranova, M. Jurásek, R. Vácha, M. Loose, I. Barák, International Journal of Molecular Sciences 22 (2021). date_created: 2021-08-15T22:01:27Z date_published: 2021-08-01T00:00:00Z date_updated: 2023-08-11T10:34:44Z day: '01' ddc: - '570' department: - _id: MaLo doi: 10.3390/ijms22158350 ec_funded: 1 external_id: isi: - '000681815400001' pmid: - '34361115' file: - access_level: open_access checksum: a4bc06e9a2c803ceff5a91f10b174054 content_type: application/pdf creator: asandaue date_created: 2021-08-16T09:35:56Z date_updated: 2021-08-16T09:35:56Z file_id: '9923' file_name: 2021_InternationalJournalOfMolecularSciences_Labajová .pdf file_size: 6132410 relation: main_file success: 1 file_date_updated: 2021-08-16T09:35:56Z has_accepted_license: '1' intvolume: ' 22' isi: 1 issue: '15' language: - iso: eng month: '08' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 2595697A-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '679239' name: Self-Organization of the Bacterial Cell publication: International Journal of Molecular Sciences publication_identifier: eissn: - '14220067' issn: - '16616596' publication_status: published publisher: MDPI quality_controlled: '1' scopus_import: '1' status: public title: Cardiolipin-containing lipid membranes attract the bacterial cell division protein diviva tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 22 year: '2021' ... --- _id: '7488' abstract: - lang: eng text: Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is associated with a recognisable facial pattern. However, the heterogeneity in causal genes and the presence of overlapping syndromes have made it increasingly difficult to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene, is having a growing impact on the diagnosis and management of genetic diseases by analysing the features of affected individuals. Here, we performed a phenotypic study on a cohort of 49 individuals harbouring causative variants in known CdLS genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within the top five predicted syndromes for 97.9% of our cases and even listed as first prediction for 83.7%. The age of patients did not seem to affect the prediction accuracy, whereas our results indicate a correlation between the clinical score and affected genes. Furthermore, each gene presents a different pattern recognition that may be used to develop new neural networks with the goal of separating different genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis based on deep learning could support the clinical diagnosis of CdLS. article_number: '1042' article_processing_charge: No article_type: original author: - first_name: Ana full_name: Latorre-Pellicer, Ana last_name: Latorre-Pellicer - first_name: Ángela full_name: Ascaso, Ángela last_name: Ascaso - first_name: Laura full_name: Trujillano, Laura last_name: Trujillano - first_name: Marta full_name: Gil-Salvador, Marta last_name: Gil-Salvador - first_name: Maria full_name: Arnedo, Maria last_name: Arnedo - first_name: Cristina full_name: Lucia-Campos, Cristina last_name: Lucia-Campos - first_name: Rebeca full_name: Antoñanzas-Pérez, Rebeca last_name: Antoñanzas-Pérez - first_name: Iñigo full_name: Marcos-Alcalde, Iñigo last_name: Marcos-Alcalde - first_name: Ilaria full_name: Parenti, Ilaria id: D93538B0-5B71-11E9-AC62-02EBE5697425 last_name: Parenti - first_name: Gloria full_name: Bueno-Lozano, Gloria last_name: Bueno-Lozano - first_name: Antonio full_name: Musio, Antonio last_name: Musio - first_name: Beatriz full_name: Puisac, Beatriz last_name: Puisac - first_name: Frank J. full_name: Kaiser, Frank J. last_name: Kaiser - first_name: Feliciano J. full_name: Ramos, Feliciano J. last_name: Ramos - first_name: Paulino full_name: Gómez-Puertas, Paulino last_name: Gómez-Puertas - first_name: Juan full_name: Pié, Juan last_name: Pié citation: ama: Latorre-Pellicer A, Ascaso Á, Trujillano L, et al. Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes. International Journal of Molecular Sciences. 2020;21(3). doi:10.3390/ijms21031042 apa: Latorre-Pellicer, A., Ascaso, Á., Trujillano, L., Gil-Salvador, M., Arnedo, M., Lucia-Campos, C., … Pié, J. (2020). Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms21031042 chicago: Latorre-Pellicer, Ana, Ángela Ascaso, Laura Trujillano, Marta Gil-Salvador, Maria Arnedo, Cristina Lucia-Campos, Rebeca Antoñanzas-Pérez, et al. “Evaluating Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes.” International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21031042. ieee: A. Latorre-Pellicer et al., “Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes,” International Journal of Molecular Sciences, vol. 21, no. 3. MDPI, 2020. ista: Latorre-Pellicer A, Ascaso Á, Trujillano L, Gil-Salvador M, Arnedo M, Lucia-Campos C, Antoñanzas-Pérez R, Marcos-Alcalde I, Parenti I, Bueno-Lozano G, Musio A, Puisac B, Kaiser FJ, Ramos FJ, Gómez-Puertas P, Pié J. 2020. Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes. International Journal of Molecular Sciences. 21(3), 1042. mla: Latorre-Pellicer, Ana, et al. “Evaluating Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes.” International Journal of Molecular Sciences, vol. 21, no. 3, 1042, MDPI, 2020, doi:10.3390/ijms21031042. short: A. Latorre-Pellicer, Á. Ascaso, L. Trujillano, M. Gil-Salvador, M. Arnedo, C. Lucia-Campos, R. Antoñanzas-Pérez, I. Marcos-Alcalde, I. Parenti, G. Bueno-Lozano, A. Musio, B. Puisac, F.J. Kaiser, F.J. Ramos, P. Gómez-Puertas, J. Pié, International Journal of Molecular Sciences 21 (2020). date_created: 2020-02-16T23:00:49Z date_published: 2020-02-04T00:00:00Z date_updated: 2023-08-18T06:35:41Z day: '04' ddc: - '570' department: - _id: GaNo doi: 10.3390/ijms21031042 external_id: isi: - '000522551606028' file: - access_level: open_access checksum: 0e6658c4fe329d55d4d9bef01c5b15d0 content_type: application/pdf creator: dernst date_created: 2020-02-18T07:49:22Z date_updated: 2020-07-14T12:47:59Z file_id: '7496' file_name: 2020_IntMolecSciences_Latorre.pdf file_size: 4271234 relation: main_file file_date_updated: 2020-07-14T12:47:59Z has_accepted_license: '1' intvolume: ' 21' isi: 1 issue: '3' language: - iso: eng month: '02' oa: 1 oa_version: Published Version publication: International Journal of Molecular Sciences publication_identifier: eissn: - '14220067' issn: - '16616596' publication_status: published publisher: MDPI quality_controlled: '1' scopus_import: '1' status: public title: Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 21 year: '2020' ... --- _id: '7664' abstract: - lang: eng text: Metabotropic γ-aminobutyric acid (GABAB) receptors contribute to the control of network activity and information processing in hippocampal circuits by regulating neuronal excitability and synaptic transmission. The dysfunction in the dentate gyrus (DG) has been implicated in Alzheimer´s disease (AD). Given the involvement of GABAB receptors in AD, to determine their subcellular localisation and possible alteration in granule cells of the DG in a mouse model of AD at 12 months of age, we used high-resolution immunoelectron microscopic analysis. Immunohistochemistry at the light microscopic level showed that the regional and cellular expression pattern of GABAB1 was similar in an AD model mouse expressing mutated human amyloid precursor protein and presenilin1 (APP/PS1) and in age-matched wild type mice. High-resolution immunoelectron microscopy revealed a distance-dependent gradient of immunolabelling for GABAB receptors, increasing from proximal to distal dendrites in both wild type and APP/PS1 mice. However, the overall density of GABAB receptors at the neuronal surface of these postsynaptic compartments of granule cells was significantly reduced in APP/PS1 mice. Parallel to this reduction in surface receptors, we found a significant increase in GABAB1 at cytoplasmic sites. GABAB receptors were also detected at presynaptic sites in the molecular layer of the DG. We also found a decrease in plasma membrane GABAB receptors in axon terminals contacting dendritic spines of granule cells, which was more pronounced in the outer than in the inner molecular layer. Altogether, our data showing post- and presynaptic reduction in surface GABAB receptors in the DG suggest the alteration of the GABAB-mediated modulation of excitability and synaptic transmission in granule cells, which may contribute to the cognitive dysfunctions in the APP/PS1 model of AD article_number: '2459' article_processing_charge: No article_type: original author: - first_name: Alejandro full_name: Martín-Belmonte, Alejandro last_name: Martín-Belmonte - first_name: Carolina full_name: Aguado, Carolina last_name: Aguado - first_name: Rocío full_name: Alfaro-Ruíz, Rocío last_name: Alfaro-Ruíz - first_name: Ana Esther full_name: Moreno-Martínez, Ana Esther last_name: Moreno-Martínez - first_name: Luis full_name: De La Ossa, Luis last_name: De La Ossa - first_name: José full_name: Martínez-Hernández, José last_name: Martínez-Hernández - first_name: Alain full_name: Buisson, Alain last_name: Buisson - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Rafael full_name: Luján, Rafael last_name: Luján citation: ama: Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, et al. Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease. International journal of molecular sciences. 2020;21(7). doi:10.3390/ijms21072459 apa: Martín-Belmonte, A., Aguado, C., Alfaro-Ruíz, R., Moreno-Martínez, A. E., De La Ossa, L., Martínez-Hernández, J., … Luján, R. (2020). Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms21072459 chicago: Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruíz, Ana Esther Moreno-Martínez, Luis De La Ossa, José Martínez-Hernández, Alain Buisson, Ryuichi Shigemoto, Yugo Fukazawa, and Rafael Luján. “Density of GABAB Receptors Is Reduced in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease.” International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21072459. ieee: A. Martín-Belmonte et al., “Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease,” International journal of molecular sciences, vol. 21, no. 7. MDPI, 2020. ista: Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Moreno-Martínez AE, De La Ossa L, Martínez-Hernández J, Buisson A, Shigemoto R, Fukazawa Y, Luján R. 2020. Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease. International journal of molecular sciences. 21(7), 2459. mla: Martín-Belmonte, Alejandro, et al. “Density of GABAB Receptors Is Reduced in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease.” International Journal of Molecular Sciences, vol. 21, no. 7, 2459, MDPI, 2020, doi:10.3390/ijms21072459. short: A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruíz, A.E. Moreno-Martínez, L. De La Ossa, J. Martínez-Hernández, A. Buisson, R. Shigemoto, Y. Fukazawa, R. Luján, International Journal of Molecular Sciences 21 (2020). date_created: 2020-04-19T22:00:55Z date_published: 2020-04-02T00:00:00Z date_updated: 2023-08-21T06:13:19Z day: '02' ddc: - '570' department: - _id: RySh doi: 10.3390/ijms21072459 external_id: isi: - '000535574200201' pmid: - '32252271' file: - access_level: open_access checksum: b9d2f1657d8c4a74b01a62b474d009b0 content_type: application/pdf creator: dernst date_created: 2020-04-20T11:43:18Z date_updated: 2020-07-14T12:48:01Z file_id: '7669' file_name: 2020_JournMolecSciences_Martin_Belmonte.pdf file_size: 2941197 relation: main_file file_date_updated: 2020-07-14T12:48:01Z has_accepted_license: '1' intvolume: ' 21' isi: 1 issue: '7' language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 publication: International journal of molecular sciences publication_identifier: eissn: - '14220067' publication_status: published publisher: MDPI quality_controlled: '1' scopus_import: '1' status: public title: Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer's disease tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 21 year: '2020' ... --- _id: '8532' abstract: - lang: eng text: The molecular anatomy of synapses defines their characteristics in transmission and plasticity. Precise measurements of the number and distribution of synaptic proteins are important for our understanding of synapse heterogeneity within and between brain regions. Freeze–fracture replica immunogold electron microscopy enables us to analyze them quantitatively on a two-dimensional membrane surface. Here, we introduce Darea software, which utilizes deep learning for analysis of replica images and demonstrate its usefulness for quick measurements of the pre- and postsynaptic areas, density and distribution of gold particles at synapses in a reproducible manner. We used Darea for comparing glutamate receptor and calcium channel distributions between hippocampal CA3-CA1 spine synapses on apical and basal dendrites, which differ in signaling pathways involved in synaptic plasticity. We found that apical synapses express a higher density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and a stronger increase of AMPA receptors with synaptic size, while basal synapses show a larger increase in N-methyl-D-aspartate (NMDA) receptors with size. Interestingly, AMPA and NMDA receptors are segregated within postsynaptic sites and negatively correlated in density among both apical and basal synapses. In the presynaptic sites, Cav2.1 voltage-gated calcium channels show similar densities in apical and basal synapses with distributions consistent with an exclusion zone model of calcium channel-release site topography. acknowledgement: "This research was funded by Austrian Academy of Sciences, DOC fellowship to D.K., European Research\r\nCouncil Advanced Grant 694539 and European Union Human Brain Project (HBP) SGA2 785907 to R.S.\r\nWe acknowledge Elena Hollergschwandtner for technical support." article_number: '6737' article_processing_charge: No article_type: original author: - first_name: David full_name: Kleindienst, David id: 42E121A4-F248-11E8-B48F-1D18A9856A87 last_name: Kleindienst - first_name: Jacqueline-Claire full_name: Montanaro-Punzengruber, Jacqueline-Claire id: 3786AB44-F248-11E8-B48F-1D18A9856A87 last_name: Montanaro-Punzengruber - first_name: Pradeep full_name: Bhandari, Pradeep id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87 last_name: Bhandari orcid: 0000-0003-0863-4481 - first_name: Matthew J full_name: Case, Matthew J id: 44B7CA5A-F248-11E8-B48F-1D18A9856A87 last_name: Case - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y, Shigemoto R. Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. International Journal of Molecular Sciences. 2020;21(18). doi:10.3390/ijms21186737 apa: Kleindienst, D., Montanaro-Punzengruber, J.-C., Bhandari, P., Case, M. J., Fukazawa, Y., & Shigemoto, R. (2020). Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms21186737 chicago: Kleindienst, David, Jacqueline-Claire Montanaro-Punzengruber, Pradeep Bhandari, Matthew J Case, Yugo Fukazawa, and Ryuichi Shigemoto. “Deep Learning-Assisted High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels at Hippocampal Synapses.” International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21186737. ieee: D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M. J. Case, Y. Fukazawa, and R. Shigemoto, “Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses,” International Journal of Molecular Sciences, vol. 21, no. 18. MDPI, 2020. ista: Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y, Shigemoto R. 2020. Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. International Journal of Molecular Sciences. 21(18), 6737. mla: Kleindienst, David, et al. “Deep Learning-Assisted High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels at Hippocampal Synapses.” International Journal of Molecular Sciences, vol. 21, no. 18, 6737, MDPI, 2020, doi:10.3390/ijms21186737. short: D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M.J. Case, Y. Fukazawa, R. Shigemoto, International Journal of Molecular Sciences 21 (2020). date_created: 2020-09-20T22:01:35Z date_published: 2020-09-14T00:00:00Z date_updated: 2024-03-27T23:30:30Z day: '14' ddc: - '570' department: - _id: RySh doi: 10.3390/ijms21186737 ec_funded: 1 external_id: isi: - '000579945300001' file: - access_level: open_access checksum: 2e4f62f3cfe945b7391fc3070e5a289f content_type: application/pdf creator: dernst date_created: 2020-09-21T14:08:58Z date_updated: 2020-09-21T14:08:58Z file_id: '8551' file_name: 2020_JournMolecSciences_Kleindienst.pdf file_size: 5748456 relation: main_file success: 1 file_date_updated: 2020-09-21T14:08:58Z has_accepted_license: '1' intvolume: ' 21' isi: 1 issue: '18' language: - iso: eng month: '09' oa: 1 oa_version: Published Version project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' - _id: 25D32BC0-B435-11E9-9278-68D0E5697425 name: Mechanism of formation and maintenance of input side-dependent asymmetry in the hippocampus - _id: 26436750-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '785907' name: Human Brain Project Specific Grant Agreement 2 (HBP SGA 2) publication: International Journal of Molecular Sciences publication_identifier: eissn: - '14220067' issn: - '16616596' publication_status: published publisher: MDPI quality_controlled: '1' related_material: record: - id: '9562' relation: dissertation_contains status: public scopus_import: '1' status: public title: Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 21 year: '2020' ... --- _id: '8283' abstract: - lang: eng text: 'Drought and salt stress are the main environmental cues affecting the survival, development, distribution, and yield of crops worldwide. MYB transcription factors play a crucial role in plants’ biological processes, but the function of pineapple MYB genes is still obscure. In this study, one of the pineapple MYB transcription factors, AcoMYB4, was isolated and characterized. The results showed that AcoMYB4 is localized in the cell nucleus, and its expression is induced by low temperature, drought, salt stress, and hormonal stimulation, especially by abscisic acid (ABA). Overexpression of AcoMYB4 in rice and Arabidopsis enhanced plant sensitivity to osmotic stress; it led to an increase in the number stomata on leaf surfaces and lower germination rate under salt and drought stress. Furthermore, in AcoMYB4 OE lines, the membrane oxidation index, free proline, and soluble sugar contents were decreased. In contrast, electrolyte leakage and malondialdehyde (MDA) content increased significantly due to membrane injury, indicating higher sensitivity to drought and salinity stresses. Besides the above, both the expression level and activities of several antioxidant enzymes were decreased, indicating lower antioxidant activity in AcoMYB4 transgenic plants. Moreover, under osmotic stress, overexpression of AcoMYB4 inhibited ABA biosynthesis through a decrease in the transcription of genes responsible for ABA synthesis (ABA1 and ABA2) and ABA signal transduction factor ABI5. These results suggest that AcoMYB4 negatively regulates osmotic stress by attenuating cellular ABA biosynthesis and signal transduction pathways. ' acknowledgement: 'We would like to thank the reviewers for their helpful comments on the original manuscript. ' article_number: '5272' article_processing_charge: No article_type: original author: - first_name: Huihuang full_name: Chen, Huihuang last_name: Chen - first_name: Linyi full_name: Lai, Linyi last_name: Lai - first_name: Lanxin full_name: Li, Lanxin id: 367EF8FA-F248-11E8-B48F-1D18A9856A87 last_name: Li orcid: 0000-0002-5607-272X - first_name: Liping full_name: Liu, Liping last_name: Liu - first_name: Bello Hassan full_name: Jakada, Bello Hassan last_name: Jakada - first_name: Youmei full_name: Huang, Youmei last_name: Huang - first_name: Qing full_name: He, Qing last_name: He - first_name: Mengnan full_name: Chai, Mengnan last_name: Chai - first_name: Xiaoping full_name: Niu, Xiaoping last_name: Niu - first_name: Yuan full_name: Qin, Yuan last_name: Qin citation: ama: Chen H, Lai L, Li L, et al. AcoMYB4, an Ananas comosus L. MYB transcription factor, functions in osmotic stress through negative regulation of ABA signaling. International Journal of Molecular Sciences. 2020;21(16). doi:10.3390/ijms21165727 apa: Chen, H., Lai, L., Li, L., Liu, L., Jakada, B. H., Huang, Y., … Qin, Y. (2020). AcoMYB4, an Ananas comosus L. MYB transcription factor, functions in osmotic stress through negative regulation of ABA signaling. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms21165727 chicago: Chen, Huihuang, Linyi Lai, Lanxin Li, Liping Liu, Bello Hassan Jakada, Youmei Huang, Qing He, Mengnan Chai, Xiaoping Niu, and Yuan Qin. “AcoMYB4, an Ananas Comosus L. MYB Transcription Factor, Functions in Osmotic Stress through Negative Regulation of ABA Signaling.” International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21165727. ieee: H. Chen et al., “AcoMYB4, an Ananas comosus L. MYB transcription factor, functions in osmotic stress through negative regulation of ABA signaling,” International Journal of Molecular Sciences, vol. 21, no. 16. MDPI, 2020. ista: Chen H, Lai L, Li L, Liu L, Jakada BH, Huang Y, He Q, Chai M, Niu X, Qin Y. 2020. AcoMYB4, an Ananas comosus L. MYB transcription factor, functions in osmotic stress through negative regulation of ABA signaling. International Journal of Molecular Sciences. 21(16), 5272. mla: Chen, Huihuang, et al. “AcoMYB4, an Ananas Comosus L. MYB Transcription Factor, Functions in Osmotic Stress through Negative Regulation of ABA Signaling.” International Journal of Molecular Sciences, vol. 21, no. 16, 5272, MDPI, 2020, doi:10.3390/ijms21165727. short: H. Chen, L. Lai, L. Li, L. Liu, B.H. Jakada, Y. Huang, Q. He, M. Chai, X. Niu, Y. Qin, International Journal of Molecular Sciences 21 (2020). date_created: 2020-08-24T06:24:03Z date_published: 2020-08-10T00:00:00Z date_updated: 2024-03-27T23:30:43Z day: '10' ddc: - '570' department: - _id: JiFr doi: 10.3390/ijms21165727 external_id: isi: - '000565090300001' pmid: - '32785037' file: - access_level: open_access checksum: 03b039244e6ae80580385fd9f577e2b2 content_type: application/pdf creator: cziletti date_created: 2020-08-25T09:53:50Z date_updated: 2020-08-25T09:53:50Z file_id: '8292' file_name: 2020_IntMolecSciences_Chen.pdf file_size: 5718755 relation: main_file success: 1 file_date_updated: 2020-08-25T09:53:50Z has_accepted_license: '1' intvolume: ' 21' isi: 1 issue: '16' language: - iso: eng month: '08' oa: 1 oa_version: Published Version pmid: 1 publication: International Journal of Molecular Sciences publication_identifier: eissn: - '14220067' issn: - '16616596' publication_status: published publisher: MDPI quality_controlled: '1' related_material: record: - id: '10083' relation: dissertation_contains status: public scopus_import: '1' status: public title: AcoMYB4, an Ananas comosus L. MYB transcription factor, functions in osmotic stress through negative regulation of ABA signaling tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 21 year: '2020' ...